Bleximenib/Venclexta Treatment Combo is Safe in Early AML Trial

Treatment with bleximenib and Venclexta (venetoclax) showed a tolerable safety profile in a phase 1b trial for patients with relapsed or refractory acute myeloid leukemia (AML), study investigator Dr. Jenny O’Nions, consultant hematologist at University College London Hospital, explained in an interview with CURE.

Findings from the clinical trial were presented at the 2025 ASH Annual Meeting.

There were no treatment discontinuations and minimal dose interruptions, highlighting beneficial tolerability. Differentiation syndrome, a potentially life-threatening side effect of menin inhibitors, was not observed. Heart-related side effects such as QTc prolongation were rare, with only one case reported that was unrelated to bleximenib.

Most side effects were low-grade cytopenias, including anemia, neutropenia and thrombocytopenia, along with mild gastrointestinal symptoms, like nausea. In the interview, O’Nions noted that these findings support further exploration of the combination’s clinical activity in this patient population, including those previously treated with Venclexta, other menin inhibitors, or prior allogeneic transplant.

These results suggest the doublet is both safe and manageable in early clinical testing.

Transcript

During your presentation, what were the most important takeaways from the safety findings?

The all-oral doublet combination of Venclexta and bleximenib had a really promising, tolerable and safe profile. There were no discontinuations of treatment and no significant dose interruptions or delays, which speaks to the tolerability. Menin inhibitors, as a class of drugs, can cause a syndrome called differentiation syndrome, which can be potentially life threatening but can very readily be managed. We did not see any reports of differentiation syndrome with bleximenib when treated in combination with venetoclax, which is encouraging.

The other safety signal that has come up with menin inhibitor drugs is the prolongation of something called QTc, which is part of the heart conduction pathway. That, again, we did not really see any significant signal of in this small cohort of patients treated with the doublet combination. There was one case of reported QTc prolongation, but that was not related to bleximenib.

Most of the side effects that were seen due to the doublet were cytopenias, including anemia, neutropenia and thrombocytopenia, and there were some gastrointestinal symptoms, mainly nausea, but no high-grade events.

Transcript has been edited for clarity and conciseness.

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